Differential Effects of Serotonin (5-HT1A and 5-HT2) Agonists and Antagonists on Renin and Corticosterone Secretion

Abstract

The present study was designed to investigate the effect of distinct serotonin (5-HT_1A and 5-HT₂) agonists and antagonists on renin and corticosterone secretion. Low doses of the selective 5-HT_1A agonists 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (5.0–500.0 µg/kg, i.p.) and ipsapirone (TVX Q 7821; 0.5–2.5 mg/kg, i.p.), and of the 5-hy-droxytryptamine (5-HT) agonist MK-212 (2.0 mg/kg, i.p.), did not elevate plasma renin activity (PRA) and concentration (PRC) 30 min postinjection. Administration of a higher dose of MK-212 (10.0 mg/kg, i.p.) and of higher doses of ipsapirone (5.0–10.0 mg/kg, i.p.), as well as the 5-HT releaser, fenfluramine (5.0 mg/kg, i.p.), resulted in large increases in PRA and PRC. The effects of MK-212 and fenfluramine on PRA and PRC were blocked by pretreatment with the selective 5-HT₂ antagonist, LY53857, in a dose-dependent (0.3–1.0 mg/kg, i.p.) manner. LY53857 (1.0 mg/kg, i.p.) by itself did not affect PRA or PRC. LY53857, furthermore, unmasked a renin-suppressive effect of MK-212, since injection of MK-212 (10.0 mg/kg, i.p.) following LY53857 administration led to a reduction in PRA and PRC. MK-212 (2.0 and 10.0 mg/kg), the high doses of 8-OH-DPAT (500.0 µg/kg), ipsapirone (1.0–10.0 mg/kg), and fenfluramine (5.0 mg/kg) all produced an increase in plasma corticosterone levels. The effects of MK-212 and fenfluramine on corticosterone were not inhibited by pretreatment with LY53857. These data suggest that 5-HTIA receptors do not play a role in the regulation of renin secretion, whereas stimulation of 5-HT2 receptors enhances renin release. The data also suggest that MK-212- and fenfluramine-induced corticosterone secretion is not mediated by 5-HT2 receptors.